Background Weight-related problems are prevalent in adolescent girls. Purpose To evaluate New Moves, a school-based program aimed at preventing weight-related problems in adolescent girls. Design School-based group-randomized controlled design. Setting/participants 356 girls (mean age=15.8±1.2 years) from six intervention and six control high schools. More than 75% of the girls were racial/ethnic minorities and 46% were overweight or obese. Data were collected in 2007-2009 and analyzed in 2009-2010. Intervention An all-girls physical education class, supplemented with nutrition and self-empowerment components, individual sessions using motivational interviewing, lunch meetings, and parent outreach. Main outcome measures Percentage body fat, BMI, physical activity, sedentary activity, dietary intake, eating patterns, unhealthy weight control behaviors, and body/self-image. Results New Moves did not lead to significant changes in the girls' percentage body fat or BMI but improvements were seen for sedentary activity, eating patterns, unhealthy weight control behaviors, and body/self-image. For example, in comparison to control girls, at 9-month follow-up, intervention girls decreased their sedentary behaviors by approximately one 30-minute block a day (p=0.050); girls increased their portion control behaviors (p=0.014); the percentage of girls using unhealthy weight control behaviors decreased by 13.7% (p=0.021); and improvements were seen in body image (p=0.045) and self-worth (p=0.031). Additionally, intervention girls reported more support by friends, teachers, and families for healthy eating and physical activity. Conclusions New Moves provides a model for addressing the broad spectrum of weight-related problems among adolescent girls. Further work is needed to enhance the effectiveness of interventions to improve weight status of youth.